[Current aspects in pediatric urolithiasis treatment]. / Aktuelle Aspekte zur Steintherapie im Kindesalter.

Compared with adults, urolithiasis is quite rare in children (1-2% of all urinary stones occur during childhood). In principle, all therapy modalities for adults can also be used in children. However, due to some anatomic and functional peculiarities in children, the differential indication for the various treatment modalities differ. As a rule, asymptomatic renal stones are not treated but observed. More urinary stones pass spontaneously in children compared with adults. If spontaneous passage is not possible or does not occur, noninvasive and minimally invasive techniques are indicated. Extracorporeal shock wave lithotripsy is the therapy of choice in most instances. Today, endoscopic techniques, however, can be safely used even in very small infants. For larger renal stones and those consisting of cysteine or whewellite, percutaneous nephrolithotomy (PCNL) is the therapy of choice, and for distal ureteral stones ureteroscopy is the method of choice. Laparoscopic and open surgery are reserved for very rare cases, especially with concomitant pathologies. Bladder calculi are treated by transurethral or suprapubic lithotripsy.

[Update of the 2Sk guidelines on the diagnostics, treatment and metaphylaxis of urolithiasis (AWMF register number 043-025) : What is new?] / Aktualisierung der S2k-Leitlinie zur Diagnostik, Therapie und Metaphylaxe der Urolithiasis (AWMF Registernummer 043-025) : Was ist neu?

The increase of medical knowledge and technical innovations together with the demographic change represent a challenge for the new conception of guidelines and clinical studies. The present S2k guidelines, which are exclusively concerned with kidney and ureteral stones, should support the treatment of urolithiasis in hospitals and private practices and provide information on urolithiasis for patients. Increasing interdisciplinary collaboration in stone treatment is also demonstrated in the number of professional and working groups participating in the update of the new guidelines. The present S2k guidelines emerged from a consensus process and demonstrate the current recommendations in step with actual practice. They provide decision-making guidance for diagnostics, treatment and metaphylactic measures based on expert opinions and available published fundamental evidence from the literature.

[Diagnostic imaging--the end of intravenous urography?]. / Bildgebende Diagnostik--das Ende des AUG?

For diagnosing patients with acute flank pain, unenhanced helical computed tomography (CT) is the most accurate method. However, conventional diagnosis using sonography and intravenous urography yields comparable results. For proper assessment, the availability, radiation dose, and cost have to be considered as well. Although the availability of CT has increased, radiation dose and cost are in favour of conventional diagnosis. At this time, we recommend sonography as the primary method. Depending on availability, intravenous urography or CT is a possible alternative.

[Economic aspects of evidence-based metaphylaxis]. / Okonomische Aspekte der evidenzbasierten Harnsteinmetaphylaxe.

The calculation model which we developed for the cost of stone therapy and metaphylaxis in Germany some years ago with a social health insurance company is based on estimates of stone incidence, types and recurrence rates, actual costs for stone removal, and metaphylaxis (based on data from a district of the social health care system). There are 200,000 stone recurrences per year in Germany. Costs for treatment of these stones amount to $687,000,000. Stone metaphylaxis reduces the recurrence rate by some 40%. The annual cost for stone removal could be lowered by $275,300,000. Metabolic evaluation/metaphylaxis amount to $70,100,000 per year, resulting in a net saving of $205,200,000. In 1997, there were 96 days off work per stone patient resulting in 5,800,000 days off work in Germany per year. Metaphylaxis is not only medically effective in stone formers but also can lower health care cost significantly. Although health care conditions may vary from country to country, in principle this calculation model is applicable also to other countries.

Pteridine and nitrite/nitrate formation in experimental septic and traumatic shock.

Bacterial lipopolysaccharides (LPS) induce the activity of guanosine triphosphate (GTP)-cyclohydrolase I (GTP-CHI), the first enzyme in the biosynthesis of tetrahydrobiopterin (H4bip) from GTP in endothelial cells and macrophages. In these and other cells, LPS also acts costimulatory with cytokines, i.e., mainly tumor necrosis factor-alpha (TNF-alpha). H4bip is the cofactor for nitric oxide synthase (NOS). We were interested in comparing the pteridine and nitrate levels in two baboon models: a hyperdynamic sepsis model and a hemorrhagic traumatic shock model. Our results show a similar response of pteridines (H4bip, neopterin) and nitrite/nitrate levels to an immune stimulus. LPS, which peaks rapidly, induces a sustained increase in pteridine levels in septic animals. Since hemorrhagic animals show very little response in terms of cytokine production, it was not possible to measure the induction of neopterin and nitrite/nitrate. This information could aid our understanding of the regulatory mechanisms in various forms of experimental shock.

Protection against endotoxemia in rats by a novel tetrahydrobiopterin analogue.

We studied the effects of a novel pterin antagonist of NO synthase, the 4-amino analogue of tetrahydrobiopterin (4-ABH4), in a rat model of endotoxic shock and compared its properties with those of N(G)-monomethyl L-arginine (L-NMMA). Treatment with a bolus dose of 4-ABH4 at 2 h after LPS challenge significantly improved the 6-day survival rate, compared with the controls treated with saline. L-NMMA treatment did not significantly influence the survival rate. This bolus treatment, using either compound, had no effect on the plasma nitrite + nitrate or plasma IL-6 levels. The continuous infusion of 4-ABH4 efficiently suppressed the enhanced calcium-dependent/independent NO synthase activities induced by endotoxin in lung homogenates and completely suppressed the increase in plasma nitrite + nitrate caused by endotoxin at 5 h, with no significant difference compared with the L- NMMA treatment. Treatment of RAW264.7 murine macrophages with 4-ABH4 but not with L-NMMA suppressed endotoxin-induced tumor necrosis factor-alpha release by the cells, whereas nitrite in the supernatant decreased in a dose-dependent fashion in both assay systems. Our data show that 4-ABH4, an inhibitor of inducible NO synthase, significantly improves survival in a rat model of endotoxic shock when administered in a bolus dose that does not reduce plasma total nitrite + nitrate levels. Because we observed no overt signs of toxicity and no influence on organ-specific tetrahydrobiopterin levels, we conclude that the novel compound 4-ABH4 is a promising drug candidate for protection against endotoxin-related mortality.

Is the determination of prostatic acid phosphatase still worthwhile in prostate cancer patients?

With the introduction of prostatic specific antigen (PSA), the role of prostatic acid phosphatase (PAP) has been questioned. Some authors still advocate its determination, because PAP may be helpful for identifying patients with organ confined cancer. Tumor progression may be detected earlier in some patients by PAP. With respect to cost, we analyzed whether PAP still has a place as a tumor marker for prostate cancer (PC). In 6,151 men seen for screening or treatment of PC or therapy of benign prostatic hyperplasia (BPH), parallel determinations of PAP and PSA were done. PC was diagnosed in 862 patients, BPH in 5,503 patients, and prostatitis in 86 patients. There were only 16 patients with PSA < 4 ng/ml and PAP > 5 ng/ml. Five of 16 patients had histologically proven BPH; 11 of 16 patients suffered from metastatic PC. Five of 11 patients were in remission on hormonal therapy; PSA had already normalized and PAP was still elevated. Three of I I patients had hormone resistant PC; PAP detected the progression earlier than PSA. In the absence of an effective treatment, this is not of clinical relevance. In 1 of 11 patients, a falsely low value was assumed. In all, 935 of 6,151 patients showed normal PAP and elevated PSA; 805 of 935 patients suffered from BPH or prostatitis; 130 of the 935 patients had PC. Stage D was found in 56 of 130 patients, stage C in 31 patients, and stage A B in 43 patients, which did not allow the identification of organ confined cancer. Therefore, there is no benefit from the determination of PAP in PC. It is both safe and cost-effective to abandon PAP as a tumor marker for PC.

Exogenous surfactant therapy in a patient with adult respiratory distress syndrome after near drowning.

A 24-year-old woman developed adult respiratory distress syndrome (ARDS) after near-drowning due to attempted suicide. Conventional mechanical ventilation together with prone positioning and inhaled nitric oxide could not provide sufficient oxygenation. Surface tension data (gamma min = 27 dyn/cm, stability index = 0.341) from a lavage sample supported the hypothesis that the surfactant function of this patient was drastically reduced due to a washout effect by aspiration of fresh water. Porcine surfactant (Curosurf, 50 mg/kg for each lung) was instilled via fibreoptic bronchoscope. The partial arterial carbon dioxide pressure (paCO2) and fraction of inspired oxygen (FiO2) ratio as well as shunt fraction (Qs/Qt) improved impressively. When respiratory situation deteriorated again, surfactant application was repeated. Altogether, six bolus instillations of surfactant (total dose 300 mg/kg = 18,000 mg) were administered until the respiratory situation had stabilized and oxygenation could be maintained by conventional mechanical ventilation. The radiological findings did not show substantial amelioration. The patient developed septic shock and died 12 days after admission. Surfactant application apparently led to a significant improvement of the respiratory function. However, the outcome could not be influenced positively. The high cost of surfactant therapy prevents the more widespread early administration in patients at risk.

New treatment modalities--the urologist's view.

Therapy of metastatic RCC is still unsatisfactory. To date, biochemotherapy with IL-2 s.c., IF a2 s.c. and 5-FU i.v. is probably the best treatment available. Response rates range between 30 and 40%. Toxicity is tolerable. Patients belonging to the low risk group, (presenting none of the following risk parameters: BSR > 70 mm, LDH > 280 U/l, neutrophilic granulocytes > 6000/microliter, hemoglobin < 10 g/l, extrapulmonary or bone metastases) show the best results. Response rates of 60% and 2-year survival rates of 65% can be achieved. When selecting candidates for biotherapy, risk parameters as mentioned above should be considered. Patients presenting these criteria do not profit from biochemotherapy. Nephrectomy in metastatic RCC is indicated in symptomatic patients. As part of an integrated treatment regimen with biotherapy in asymptomatic patients, nephrectomy should be performed only after response to biotherapy. These patients show a long-lasting progression-free survival. A randomized study proving the benefit of cytoreductive surgery, however, does not exist. Experimental research recently developed numerous strategies for potential therapy. The most interesting and hopeful starting points are gene manipulation and angiogenesis. Clinical trials, however, have to be awaited.

Mechanical properties of the lungs of posttraumatic rats are improved by including fat in total parenteral nutrition.

Posttraumatic lung failure is often associated with alterations in lung surfactant composition and function. Our previous studies with total parenteral nutrition (TPN) have shown the effect of fat supply on phospholipid composition in pulmonary surfactant. Consequently, we attempted to determine whether fat supply would also improve the functional properties of the lung and surfactant. After polytrauma consisting of laparotomy, hypovolemia, and a single femur fracture, the animals were fed only parenterally for 14 days. Two groups of rats were infused via the jugular vein with isocaloric (260 kcal/kg/day) and isonitrogenous (5.62 gN/kg/day) regimens. The nonprotein calories were given either as glucose alone or 30% of calories as fat. Lung function was assessed by measurement of static lung compliance and total lung capacity. Surfactant isolated from lavage fluid was evaluated by means of a Wilhelmy balance. In agreement with our previous studies, in which we obtained a higher level of saturated lecithin in the fat groups, we found significantly (p less than 0.05) increased compliance (2.93 +/- 0.54 ml/cm H2O/kg BW) in the fat group compared to the carbohydrate group (2.02 +/- 0.36 ml/cm H2O/kg BW). Furthermore, a significantly (p less than 0.05) elevated total lung capacity was noted in the fat group (32.60 +/- 3.90 vs 26.00 +/- 1.45 ml/kg BW). The relatively improved surface tension properties as expressed by stability index (S = 0.89 +/- 0.24 vs 0.66 +/- 0.22) and minimum surface tension (gamma min = 18.5 +/- 5.01 vs 20.75 +/- 2.81) is a characteristic change, and was seen in the fat group.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of parenteral nutrition on phospholipid metabolism in posttraumatic rat lungs.

In the current investigation, we studied two groups of rats--one group supplied exogenous phospholipid precursors (carbohydrate plus fat emulsion group) and the other given only calories (carbohydrate group)--to evaluate the effects on surfactant composition by normocaloric alimentation, using a hypovolemic-traumatic shock model. The total phospholipid (PHL) contents of lung tissue were similar in both groups. However, we found differences in the dipalmitoylphosphatidylcholine fraction (DPPC--the most important component of surfactant material) in both lung tissue and lavage fluid. With lipid emulsion, there was an increased fraction of saturated lecithins (mainly DPPC) both in lung tissue and lavage fluid, similar to former studies with hypocaloric alimentation. In this model, those findings suggest that the PHL pattern does not depend on the quantity of caloric supply, but, rather, on the infusion composition. The enhanced DPPC content is further reflected in improved surfactant status: lipid in parenteral nutrition (PN) may exert a direct salutary effect on lung mechanics.

Influence of vitamin A deficiency on the excretion of uromucoid and other substances in the urine of rats.

Male Fü-albino rats were weaned at the age of four weeks and maintained on a vitamin A-deficient diet. When they were 14-18 and 21-26 weeks old, the concentration of uromucoid, calcium and other substances possibly important for the pathogenesis of urinary calculi were determined. Reduced uromucoid excretion with hypercalciuria and reduced phosphate levels were observed. Subsequent examination of the kidneys did not demonstrate the presence of nephrocalcinosis or lithiasis. The relation between vitamin A, the synthesis of uromucoid and AMPS and calcium metabolism in the renal tubules is discussed.

Verapamil limits shockwave-induced renal tubular damage in vivo.

Previous investigations on Madin Darby Canine Kidney (MDCK) cells demonstrated the protective effect of verapamil against shockwave-induced tubular dysfunction. In the present study, we investigated whether verapamil is also protective against shockwave-induced damage in vivo. Male rates were randomly assigned to three groups: verapamil (N = 18) (Group I), control (N = 18) (Group II), or sham treatment (N = 4) (Group III). Groups I and II were treated with 500 shockwaves to each kidney with the Dornier MFL 5000 at 18 kV. Animals assigned to Group III received only anesthesics. Verapamil was given to the animals in Group I for 5 days starting 1 day before shockwave exposure. Urine was collected for 8 hours the day before and immediately, 1.7, and 28 days after shockwave exposure (SWE) for measurement of volume, osmolality, hemoglobin, protein, N-acetyl-beta-glucosaminidase (NAG), beta 2-microglobulin (beta 2M), sodium, and creatinine. Kidneys were perfused and removed for histologic study 1, 7, and 28 days after SWE in six animals of Groups I and II. Blood was taken in these rats (Day 1 after SWE) for the determination of creatinine and sodium and the calculation of the creatinine clearance (CCr) and the fractional excretion of sodium (FENa). After SWE, there was strong diuresis and significantly increased excretion of NAG and beta 2M in the controls, while urine osmolality decreased. These changes were significantly less pronounced in the verapamil-treated rats. The CCr was higher and FENa lower than in the latter group.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal phosphatidylcholine composition of lung surfactant 24 hours after inhalation injury.

The effects of cotton smoke injury on the phosphatidylcholine composition of pulmonary surfactant material were studied. While under halothane anesthesia, 18 ewes were intubated using a double-lumen tube. In six sheep the left lung was exposed to smoke; in another six sheep the right lung was exposed to smoke. A sham group of six sheep was insufflated with air instead of smoke. Twenty-four hours later the animals were killed, and alveolar lavage fluid was obtained from both lungs. Phospholipid material was separated, and its relative phosphatidylcholine composition was determined. In the smoke-treated lungs this composition was not different statistically when compared with the contralateral and the sham-exposed lungs. These findings suggested that smoke inhalation has no effect on the composition of the phosphatidylcholine fraction in the alveolar lining layer 24 hours after injury.

[Socioeconomic aspects of urinary calculi and metaphylaxis of urinary calculi]. / Volkswirtschaftliche Aspekte des Harnsteinleidens und der Harnsteinmetaphylaxe.

A calculation model was developed for the cost of stone therapy and metaphylaxis in Germany based on estimates of stone incidence, types and recurrence rates, actual costs for stone removal and metaphylaxis (based on data from a district of the social health care system). There are 200,000 stone recurrences per year in Germany. Cost for treatment of these stones amount to $687,000,000. Stone metaphylaxis reduces the recurrence rate by some 40%. The annual cost for stone removal could be lowered by $275,300,000. Metabolic evaluation/metaphylaxis amount to $70,100,000 per year, resulting in an net saving of $205,200,000. In 1997, there were 96 days off-work per stone patient resulting in 5,800,000 days off-work in Germany per year. Metaphylaxis in stone formers can lower health care cost significantly. Although health care conditions may vary from country to country, in principle this calculation model is applicable also to other countries.

[Studies of calcium metabolism in normal persons and patients with hypercalciuria in relation to therapy with the dietary fiber preparation Farnolith]. / Kalziumstoffwechseluntersuchungen bei Normalpersonen und Hyperkalziurikern unter Therapie mit dem Ballaststoffpräparat Farnolith.

Farnolith (a dietary fibre preparation) was given to normal patients (n = 6) with absorptive hypercalciuria type I (n = 6) and to one patient with renal hypercalciuria. Farnolith binds calcium and reduces calcium absorption in the intestines. In normal subjects, the urine and serum parameters of calcium metabolism (total and ionized calcium, 1.25-dihydroxy-vitamin D) were unchanged. In absorptive hypercalciuria type I, a significant decrease in calcium excretion was achieved; oxalate excretion decreased as well. Low PTH values normalized; vitamin-D metabolites were not affected. In renal hypercalciuria, PTH and 1.25 DHCC were increased, whereas hypercalciuria persisted. Our investigations show that Farnolith is a reasonable treatment for absorptive hypercalciuria. Calcium homeostasis is rendered normal by Farnolith without producing secondary hyperoxaluria as sodium cellulose phosphate. Patients with primary renal calcium leakage and secondary hyperparathyroidism should not be treated with Farnolith.

[Studies of calcium metabolism in patients with hypercalciuria]. / Kalziumstoffwechseluntersuchungen bei Patienten mit Hyperkalziurie.

The different subgroups of hypercalciuria cannot be separated clearly by the Pak calcium-load test. To improve the diagnosis and therapy we examined all relevant parameters of calcium metabolism in 32 patients with calcium urolithiasis and hypercalciuria (> 6.25 mmol/day). We also conducted bone mineral density measurements as well as the Pak calcium-load test. In most cases the pathophysiological constellations which Pak takes as the basis for his classification of hypercalciuria could not be shown. To date, diagnostics only insufficiently explains the genesis of hypercalciuria (except pHPT). As a consequence, a therapeutic problem arises: a low-calcium diet should not be generally recommended, since some patients may develop osteopenia. From our investigation the following diagnostic and therapeutic conclusions can be drawn: (1) Hypercalciuria in primary hyperparathyroidism should be treated by surgical removal of the adenoma. (2) The parathormone-independent osteogenic form should be treated with thiazides. (3) Hypercalciuria with increased 1.25-dihydroxyvitamin D should be treated by low-calcium diet.

[Results of color-coded duplex ultrasound diagnosis (angiodynography) after intraurethral administration of PgE1 in erectile dysfunction]. / Ergebnisse der Color-coded-duplex-Sonographie (Angiodynographie) nach intraurethraler Applikation von Pg E1 bei ED.

When the pathomechanism of erectile dysfunction is obscure, intraurethral administration of prostaglandin E1 is followed by a marked increase in blood flow velocity in the penile arteries as measured by color-coded Duplex sonography. This increase compares to that following intracavernous administration of half the dose of prostaglandin E1. The difference in the effects after intraurethral and intracavernous administration is the missing rigidity after intraurethral application; there must be a loss of pharmacological efficacy to the smooth penile muscles. Clinical efficacy is to be expected with higher intraurethral dosage.

[Local hyperthermia in benign prostatic hyperplasia]. / Lokale Hyperthermie bei benigner Prostatahyperplasie.

In recent years, hyperthermia has been used for the treatment of benign prostatic hyperplasia (BPH). The preliminary results reported were promising. Except for patients with total urinary retention, however, objective voiding parameters have not been reported in detail for patients with "prostatism". In a phase II study we treated 30 patients with BPH by local microwave hyperthermia (915 MHz). The prostate was heated transrectally to 42-43 degrees C in eight sessions of 60 min each. The sessions were given twice a week. To assess the results of the treatment the following parameters were determined before and 4 weeks after hyperthermia therapy: transrectal ultrasound of the prostate with volumetry, urinary flow rate, and residual volume. In all, 28 patients were evaluatable. Only 2/28 showed clinical improvement. Neither the voiding parameters nor the size of the prostate were significantly changed by hyperthermia. The success rate of 7.1% is even lower than the spontaneous temporary regression rate of BPH. Thus, to our mind, hyperthermia cannot be regarded an effective treatment comparable to TUR for BPH.

[Local hyperthermia in prostate cancer]. / Lokale Hyperthermie beim Prostatakarzinom.

We conducted a clinical trial evaluating the effects of hyperthermia in patients with carcinoma of the prostate, treating 20 patients with newly diagnosed carcinoma of the prostate with local microwave hyperthermia (915 MHz). Histological examination revealed hypoeremic effects and diffuse oedema with interstitial lymphoplasmatic cellular infiltration. However, necrotic tumour cells were not found in any of specimens. A second series consisted of 10 patients with metastasizing carcinoma of the prostate (n = 4 untreated; n = 6 hormone-resistant). For 8 weeks, epirubicin was administered once weekly, followed each time by local microwave hyperthermia 1 h later. The efficacy was evaluated according to the EORTC criteria. In 4 patients with untreated carcinoma no change was found in the size of the prostate or metastases. In 3 of the 6 patients with hormone-resistant carcinoma progressive disease was found, while the other 3 had stable disease. Only in 2 of the 10 patients did the grading of tumour regression reveal any improvement. Cytophotometric studies showed no change of DNA ploidy. Currently we consider hyperthermia unsuitable as monotherapy for carcinoma of the prostate, and the combination of epirubicin and hyperthermia is no more favourable than monotherapy with epirubicin alone. Further studies are necessary to evaluate other cytotoxic regimens and various patterns of application for hyperthermia.